白介素-1β对高糖刺激的人肾小管上皮细胞转分化的影响

目的探讨炎症细胞因子白介素-1β（interleukin-1βIL-1β）对高糖刺激的人肾小管上皮细胞转分化的影响。-方法体外培养人肾近曲小管上皮细胞株（HKCs）,随机分为正常对照组（5.5 mmol/L normal glucose）;高糖组（30 mmol/L high glucose）;高糖＋IL-1β（5ng/ml）组。分别于处理后24h、48h、72h收集细胞,采用免疫细胞化学染色和Western蛋白印迹法检测细胞角蛋白-18（cytokeratin-18 CK-18）、α-平滑肌肌动蛋白（α-smooth muscle actinα-SMA）水平。结果高糖能够诱导肾小管上皮细胞α-SMA蛋白的合成增加,而肾小管上皮细胞的标志物CK-18的表达逐渐减少;IL-1β与高糖同时刺激可使肾小管上皮细胞α-SMA蛋白表达进一步增多,而其自身标志物CK-18的表达则明显下降。结论炎症因子IL-1β能增强高糖对肾小管上皮细胞转分化的作用。     

Moxostoma的磷酸葡萄糖异构酶电泳研究

用水平淀粉凝胶电泳对290尾Moxostoma属3个种的胭脂鱼进行了磷酸葡萄糖异构酶(PGI)的研究,得到10种电泳表现型(Phenotype),由A与B两个位点控制。A位点向阳极迁移,有a、b、c、d及e5个等位基因;B位点向阴极迁移,有f及g两个等位基因。种间差异明显。 不同采集地区(德克萨斯、佛罗里达及路易斯安那)的鱼类,新鲜材料、冰冻材料及雌雄之间电泳结果无差异。     

基于交叉抚育的雄性根田鼠对异性同胞尿气味的识别

通过交叉抚育建立室内繁殖种群,在断奶后（80日龄）分别取这些供体的新鲜尿气味作刺激物,在行为观察箱中观察和记录雄性根田鼠对雌鼠气味的行为反应,以研究根田鼠同胞识别的化学通讯机制。结果表明：①在不同的发育时期（2～70日龄）,雄性同巢同胞与异巢同胞的体重没有显著差异。②雄性根田鼠对雌性同巢非同胞气味的接近潜伏期显著长于对异巢非同胞的接近潜伏期（P〈0．05）,其对异巢非同胞气味的访问时间和嗅舔时间都显著高于同巢非同胞气味（P〈0．05）。③雄性根田鼠对雌性异巢同胞和异巢非同胞气味的不存在明显偏好。其对两者的接近潜伏期、访问频次、访问时间、嗅舔频次和嗅舔时间等行为响应均无显著差异（P〈0．05）。这些结果表明,80日龄时,雄性根田鼠能够识别熟悉和陌生的无亲属关系雌性尿气味,但不能区分陌生的亲属和非亲属,因此,其异性同胞识别的机制为共生熟悉模式。     

Bacteriophage T4 DNA polymerase determines the amount and specificity of ultraviolet mutagenesis

Summary Ultraviolet mutagenesis in bacteriophage T4 proceeds via error-prone repair (EPR) and requires the functional integrity of the uvsWXY system which mediates genetic recombination, recombinational repair, and mutability by diverse DNA damaging agents. Current opinion holds that mutagens acting through EPR generate DNA damage which blocks the progress of the replication complex and that EPR consists of the facilitated bypass of such inaccurate, damaged templates. This notion predicts that the T4 DNA polymerase (encoded by gene 43) mediates EPR in UV irradiated phage T4. This prediction is verified by the discovery that gene 43 mutations often enhance or reduce UV mutagenesis (which is scored by the induction of r mutants) and sometimes change its specificity.     

The isolation of apparently homoplastidic mutants induced by a nuclear recessive gene in Arabidopsis thaliana

Summary The nuclear recessive gene, chm1, of Arabidopsis thaliana is a imitator that induces a variety of plastid alterations giving rise to mixed cells and variegated leaves. The variegation is maternally transmitted but chm1 is transmitted in a Mendelian fashion (Rédei 1973; Rédei and Plurad 1973). In order to characterize the different types of plastid alterations induced by chm1, isolating homoplastidic lines, each apparently containing one type of mutant plastid in its cells, was essential since such characterization cannot be carried out on mixed cells. We have used two genetic approaches to isolate several apparently homoplastidic mutant lines by the removal of the mutator from the genetic background, and the maternal transmission of the mutant plastids. The rapidity of obtaining homoplastidic lines in the absence of chm1 indicated a non-stochastic sorting-out of plastids in mixed cells. That each of the chm1-free homoplastidic mutant lines was apparently homoplastidic for one type of mutant plastids was confirmed by electron microscopic observations. Here we report, for the first time, the production of different homoplastidic lines in the absence of the nuclear-mutator gene. Such genetically-stable homogeneous material should be a useful tool for studying the molecular mechanism(s) by which chm1 induces a variety of heritable plastid alterations.     

Validation of a urine metabolome fingerprint in dog for phenotypic classification

Selective breeding of dogs over hundreds of years has inadvertently resulted in breed-specific propensities to particular diseases. Furthermore, it has likely induced more subtle affects on the physiology of certain breeds and moved them from their evolutionary optima. In the absence of obvious disease phenotypes such subtle changes could have yet unrecognised breed-specific implications for health and well-being. Here we have applied NMR metabolomics as a discovery-driven approach to identify the impact of breed on the urinary profile of dog and to determine if non-disease-related breed differences can be identified. Multiple urines were collected non-invasively over a two-week period from seven neutered male Labrador retrievers and miniature Schnauzers. Following NMR analyses by 1-dimensional ¹H and 2-dimensional ¹H J-resolved (JRES) spectroscopy, principal component analysis revealed that the metabolic variability within each individual is relatively small compared to inter-individual variability, and that some separation between breeds was evident. A supervised model, using partial least squares discriminant analysis (PLS-DA) with class based upon breed, was trained using the JRES data. The model predicted correctly the breed of seven additional urines, yielding a model sensitivity and specificity of 100%. Several significant metabolic differences between the breeds were identified. A second model was developed using PLS-DA with class based upon individual dogs, which again achieved high classification accuracy for the test set. Overall, this confirms that canine urine is information-rich and that breed is a major determinant of urinary metabolic fingerprints. In the future this may enable a more accurate development of specific nutritional care for an individual or breed.     

肿瘤干细胞及其模型的研究现状及临床治疗最新进展

癌症发生最有名的模型之一肿瘤CSCcancer stem cell(CSC)模型已经被确立为一种细胞机制,有助于体现不同类型的肿瘤表型和功能的异质性。然而,最新研究突出显示了肿瘤CSC模型的复杂性和挑战性:CSC表型在不同的病人间有本质上的不同,肿瘤可能含有多种表型或遗传上不同的CSC,转移的肿瘤CSC可能由原始肿瘤CSC进展而来,肿瘤细胞可进行可逆的表型的改变。虽然在特定情况下,肿瘤CSC的概念具有临床相关性,但越来越多的证据表明,定位、鉴定出肿瘤灶中所有亚型的肿瘤CSC将对临床上预防肿瘤复发具有特殊意义。有以下几个因素可以促使异质性的发生:基因突变,后生的变化,与微环境间的相互作用以及存在或缺失细胞分级等。肿瘤异质性可以用不同的细胞机制来解释。虽然CSC具有CSC自我更新和分化的特性,但是它们不一定是正常组织CSC转化而形成的。这种CSC模型引起了科研工作者广泛的关注,我们结合新近的相关文献综述如下。     

Endoplasmic reticulum stress controls M2 macrophage differentiation and foam cell formation

Macrophages are essential in atherosclerosis progression, but regulation of the M1 versus M2 phenotype and their role in cholesterol deposition are unclear. We demonstrate that endoplasmic reticulum (ER) stress is a key regulator of macrophage differentiation and cholesterol deposition. Macrophages from diabetic patients were classically or alternatively stimulated and then exposed to oxidized LDL. Alternative stimulation into M2 macrophages lead to increased foam cell formation by inducing scavenger receptor CD36 and SR-A1 expression. ER stress induced by alternative stimulation was necessary to generate the M2 phenotype through JNK activation and increased PPARγ expression. The absence of CD36 or SR-A1 signaling independently of modified cholesterol uptake decreased ER stress and prevented the M2 differentiation typically induced by alternative stimulation. Moreover, suppression of ER stress shifted differentiated M2 macrophages toward an M1 phenotype and subsequently suppressed foam cell formation by increasing HDL- and apoA-1-induced cholesterol efflux indicating suppression of macrophage ER stress as a potential therapy for atherosclerosis.     

From heterogeneity to plasticity in adipose tissues: site-specific differences

In mammals, two types of adipose tissues are present, brown (BAT) and white (WAT). WAT itself can be divided into subcutaneous and internal fat deposits. All these tissues have been shown to present a great tissue plasticity, and recent data emphasized on the multiple differentiation potentials obtained from subcutaneous WAT. However, no study has compared the heterogeneity of stroma-vascular fraction (SVF) cells and their differentiation potentials according to the localization of the fat pad. This study clearly demonstrates that WAT and BAT present different antigenic features and differentiation potentials. WAT by contrast to BAT contains a large population of hematopoietic cells composed essentially of macrophages and hematopoietic progenitor cells. In WAT, the non-hematopoietic population is mainly composed of mesenchymal stem cell (MSC)-like but contains also a significant proportion of immature cells, whereas in BAT, the stromal cells do not present the same phenotype. Internal and subcutaneous WAT present some discrete differences in the phenotype of their cell populations. WAT derived SVF cells give rise to osteoblasts, endothelial cells, adipocytes, hematopoietic cells, and cardiomyoblasts only from inguinal cells. By contrast, BAT derived SVF cells display a reduced plasticity. Adipose tissues thus appear as complex tissues composed of different cell subsets according to the location of fat pads. Inguinal WAT appears as the most plastic adipose tissue and represents a potential and suitable source of stem cell, considering its easy sampling as a major advantage for cell therapy.